March 6, 2017
Merck & Co. issued results of a phase III study of letermovir for the prevention of clinically significant cytomegalovirus (CMV) infection in adult (18 years and older) CMV-seropositive recipients of an allogeneic hematopoietic stem cell transplant (HSCT), also known as bone marrow transplant (BMT). CMV seropositive HSCT recipients who had undetectable plasma CMV DNA within five days of randomization were eligible for the study. Patients were randomized in a 2:1 ratio to receive either letermovir or placebo administered once daily, either in oral tablet or intravenous formulation, through week 14 (day 100) post-HSCT. Letermovir was dosed at 480mg/day (or 240mg/day if the patient was on the immunosuppressant medication cyclosporine). Letermovir was started after HSCT, as early as the day of transplant and no later than 28 days post-transplant. The study met its primary efficacy endpoint, showing that of 495 treated patients who had undetectable CMV DNA at the start of study treatment, significantly fewer patients developed clinically significant CMV infection in the letermovir arm (37.5%, n=122/325) compared to the placebo arm (60.6%, n=103/170) through week 24 post-HSCT [treatment difference: -23.5 (95% confidence interval -32.5 to -14.6), one-sided p<0.0001]. In addition, a secondary endpoint evaluating the end-of-treatment period (at week 14 post-HSCT) showed that significantly fewer patients developed clinically significant CMV infection in the letermovir arm (19.1%, n=62/325) compared to the placebo arm (50.0%, n=85/170) through week 14 (day 100) post-HSCT [treatment difference: -31.3 (95% confidence interval -39.9 to -22.6), one-sided p<0.0001]. In this study, letermovir was associated with lower all-cause mortality through week 24 post-HSCT (9.8%, n=32/325) compared to placebo (15.9%, n=27/170), log-rank two-sided p=0.0317. The company will submit regulatory applications for letermovir in 2017.
October 14, 2013
Chimerix reported results of a phase II trial CMX001-201 evaluating brincidofovir (CMX001) for the prevention of cytomegalovirus (CMV) infection in hematopoietic cell transplant (HCT) recipients. In the 230-subject, randomized, placebo-controlled, double-blind, dose-escalation study, subjects were randomized into five sequential, dose-escalating cohorts to receive either brincidofovir or placebo, at doses ranging from 40mg once weekly to 200mg twice weekly. Subjects were treated for nine to 11 weeks through post-transplant week 13, after which subjects were followed for an additional four to eight weeks. The proportion of subjects who developed CMV disease or a CMV PCR positive result at the end of the 100mg twice weekly dosing period was 10% (five of 50) v. 37% (22 of 59) in the placebo-treated group (p=0.002). In a pre-specified subgroup of subjects who were CMV PCR negative at baseline (the subject population being enrolled in SUPPRESS), zero of 41 subjects in the brincidofovir 100mg twice weekly group developed CMV PCR of >= 1,000copies/mL during the dosing period, compared to 15 of 47 subjects (32%) in the placebo group. Chimerix recently initiated the phase III trial of brincidofovir 100mg twice weekly.
February 20, 2012
AiCuris reported results from a phase IIb trial of letermovir for the prevention of human cytomegalovirus (HCMV) following bone marrow transplantation. This randomized, double-blind, placebo controlled trial enrolled 133 subjects undergoing allogeneic stem cell transplant. The subjects received one of three doses of letermovir or placebo for 12 weeks. The primary endpoints were the incidence and time to onset of HCMV prophylaxis failure. Two doses of letermovir, 120 mg and 240 mg once daily for 84 days, meet both primary efficacy endpoints with high statistical significance versus placebo. The incidence of failure due to efficacy failure of prophylaxis or due to discontinuation of treatment was significantly lower in the Letermovir 240 mg/day (29.4%; p≡0.007) and 120 mg/day (32.3%; p≡0.014) groups compared to placebo (63.6%). The incidence of HCMV prophylaxis failure among subjects receiving treatment for at least seven days prior to HCMV replication was none for Letermovir 240 mg (p≡0.004 vs. placebo) and two subjects for the 120 mg group (p≡0.109 vs. placebo). Similarly, the time to onset of prophylaxis failure among subjects receiving 240 mg/day of Letermovir was significantly different (p≡0.02) compared to those receiving placebo. All doses were safe and well tolerated.
February 13, 2012
Chimerix issued results from a phase II trial of CMX001 for the prevention of cytomegalovirus (CMV) disease in hematopoietic stem cell transplant (HCT) recipients. This randomized, double-blind, placebo-controlled, dose-escalation study (Study 201) enrolled 230 CMV seropositive allogeneic stem cell transplant recipients. Following engraftment, subjects were stratified based on the presence or absence of acute GVHD and CMV DNA in plasma. They were then placed into five sequential, dose-escalating cohorts and were treated once or twice weekly for 9 to 11 weeks through post-transplant Week 13. Results from subjects receiving CMX001 100 mg twice weekly met the primary endpoint, a statistically significant reduction in CMV viremia (CMV>200 copies/mL) or disease at the end of treatment versus those who received placebo (p≡0.001). Three different doses of CMX001 demonstrated statistically significant reductions in the proportion of subjects with CMV viremia>1000 copies/mL at any time during treatment when compared to placebo (p≡0.002, <0.001, <0.001, respectively). In subjects who were CMV viremia negative prior to treatment, four different CMX001 dose regimens (100 mg and 200 mg once weekly and twice weekly) demonstrated statistically significant reduction versus placebo.
July 13, 2009
Vical reported positive interim results from a phase II trial of TransVax, a vaccine for the treatment of cytomegalovirus (CMV). This two-arm, double-blind, placebo-controlled multi-center study enrolled 80 donor/recipient stem-cell-transplant patient pairs across sites in the US. In one arm, vaccine or placebo was administered to both the donors and recipients (the donor-recipient arm). In the other arm vaccine or placebo was administered only to the stem cell transplant recipients (the recipient-only arm). The trial was designed to evaluate the potential of TransVax to prevent CMV reactivation in immunosuppressed CMV-seropositive hematopoietic stem cell transplant (HCT) recipients. Data are from a four month analysis. At the four-month time-point, TransVax demonstrated a clear reduction compared with placebo in the percentage of recipients experiencing CMV reactivation. TransVax also showed a decrease in recurrence of CMV reactivation, a delay in time to initial detectable viremia, a decrease in duration of viremia, and decreases in peak and cumulative viral loads. An overall increase in cellular immune responses compared with placebo was also observed.
February 16, 2009
ViroPharma released negative results from a phase III trial of maribavir for the prevention of cytomegalovirus (CMV) disease in recipients of allogeneic stem cell transplants. This randomized, double-blind, placebo-controlled, multi-center study enrolled 500 subjects who had undergone allogeneic stem cell transplantation. Following transplantation, subjects were randomized to receive maribavir (100mg twice daily) or matching placebo for a maximum duration of 12 weeks. They were to undergo testing for CMV infection at least once a week. The primary efficacy endpoint was the incidence of CMV disease within 180 days post-transplant. Secondary endpoints included incidence of initiation of preemptive anti-CMV therapy, incidence of graft-versus-host disease, mortality and CMV disease-free survival. The primary endpoint was not reached; there was no statistically significant difference between maribavir and placebo in reducing the rate of CMV disease. In addition, the study failed to reach the secondary endpoints. The incidence of CMV disease within 6 months was 4.4% for maribavir compared to 4.8% for placebo (p≡0.79). The rate of initiation of anti-CMV treatment within six months, which was 37.9% for maribavir compared to 40.5% for placebo (P≡0.49). In addition, the incidence of graft-versus-host disease, mortality and CMV disease-free survival was comparable between the groups.
November 17, 2008
Vical issued positive interim results from a phase II trial of VCL-CB01, their DNA vaccine for the prevention of cytomegalovirus (CMV). This two-arm, double-blind, placebo-controlled multi-center study enrolled 80 donor/recipient stem-cell-transplant patient pairs across sites in the US. In one arm, vaccine or placebo was administered to both the donors and recipients (the donor-recipient arm). In the other arm vaccine or placebo was administered only to the stem cell transplant recipients (the recipient-only arm). Interim data are from the first 33 transplant recipients in the recipient-only arm. Analysis of immunogenicity showed significant post-transplant enhancement of CMV-specific T-cell responses to the two CMV antigens targeted by the vaccine: pp65 (p<0.05) and gB (p<0.05) in subjects receiving vaccine compared with placebo.